Assistant Professor of Biology
Ph.D. Mount Sinai School of Medicine, 1998
Areas of interest: molecular and cellular basis of synaptic function and alzheimer’s disease
Brain function requires proper networking and communication between neurons. In Alzheimer’s disease (AD), there is a widespread cognitive decline causing problems with memory, thinking, and behavior. The focus of our research is to study cellular and molecular pathways involved in Alzheimer’s pathogenesis. We will examine Alzheimer’s related proteins by integrating mouse genetics with biochemical and cell biological approaches to address the physiological function and pathological processes that lead to neurodegeneration in the AD brain.
One of the pathological hallmarks of AD is the formation of extracellular neuritic plaques containing deposits of 40-43 amino acid amyloid peptides that are derived from the parent amyloid precursor protein (APP). APP is a member of the highly conserved APP gene family and an integral membrane glycoprotein that is physiologically processed by site-specific proteases. To date, the normal biological function of the APP gene family remains unclear. We will investigate the role of the APP gene family in development, specifically on synaptic function and learning, and more importantly, their native function in the adult brain.
Our second interest focuses on an essential family of neuronal adaptor proteins named Mint/X11s that have been implicated in coupling synaptic functions to the regulation of amyloidogenic processing of APP. To better understand Mint-APP biology in AD, we have created mice lacking Mint proteins combined with transgenic mouse models of AD. We found that deletion of Mint proteins delays the age-dependent production of amyloid pathology associated with AD. We are currently determining the novel mechanism by which Mint proteins alter APP cleavage.
- BI 325 Principles of Neurobiology
- BI481 Molecular Biology of the Neuron
- BI582 Seminar in Biology - Neurodegeneration
- Beffert U, Dillon GM, Sullivan JM, Stuart CE, Gilbert JP, Kambouris JA, Ho A (2012) Microtubule plus-end tracking protein CLASP2 regulates neuronal polarity and synaptic function. Journal of Neuroscience, 32: 13906-13916.
- Chaufty J, Sullivan SE, Ho A (2012) Intracellular APP sorting and Aß secretion are regulated by src-mediated phosphorylation of Mint2. Journal of Neuroscience, 32: 9613-9625.
- Matos MF, Xu Y, Dulubova I, Otwinowski Z, Richardson III JM, Tomchick DR, Rizo J, Ho A (2012) Autoinhibition of Mint1 adaptor protein regulates APP binding and processing. Proceedings National Academy Sciences USA 109: 3802-3807.
- Ho A and Shen J (2011) Presenilins in synaptic function and disease. Trends in Molecular Medicine 17: 617-624.
- Ho A, Liu X, Südhof TC (2008) Deletion of Mint proteins decreases amyloid production in transgenic mouse models of Alzheimer’s disease. Journal of Neuroscience 28: 14392-14400.
- Ho A, Morishita W, Atasoy D, Liu X, Tabuchi K, Hammer RE, Malenka RC, Südhof TC (2006) Genetic analysis of Mint/X11 proteins: Essential presynaptic functions of a neuronal adaptor protein family. Journal of Neuroscience 26:13089-13101.
- Ho A, Südhof TC (2004) Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage. Proceedings of the National Academy Sciences 101:2549-2553.
- Ho A, Morishita W, Hammer RE, Malenka RC, Südhof TC (2003) A role of Mints in transmitter release: Mint 1 knockout mice exhibit impaired GABAergic synaptic transmission. Proceedings of the National Academy Sciences 100:1409-1414.